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The development of targeted alpha therapy (TAT) as a viable cancer treatment requires innovative solutions to challenges associated with radionuclide retention to enhance local tumor cytotoxicity and to minimize off-target effects. Nanoparticles (NPs) with high encapsulation and high retention of radionuclides have shown potential in overcoming these issues. This article shows the influence of pH on the structure of lanthanum vanadate (LaVO4) NPs and its impact on the radiochemical yield of 223Ra and subsequent retention of its decay daughters, 211Pb and 211Bi. An acidic pH (4.9) results in a high fraction of La(223Ra)VO4 NPs with tetragonal structure (44.6&ndash, 66.1%) and a 223Ra radiochemical yield &lt, 40%. Adjusting the pH to 11 yields &gt, 80% of La(223Ra)VO4 NPs with monoclinic structure and increases the 223Ra radiochemical yield &gt, 85%. The leakage of decay daughters from La(223Ra)VO4 NPs (pH 11) was &lt, 5% and &lt, 0.5% when exposed to deionized water and phosphate-buffered saline, respectively. Altering the surface chemistry of La(223Ra)VO4 NPs with carboxylate and phosphate compounds resulted in a threefold decrease in hydrodynamic diameter and a 223Ra radiochemical yield between 74.7% and 99.6%. These results show the importance of tailoring the synthesis parameters and surface chemistry of LaVO4 NPs to obtain high encapsulation and retention of radionuclides.

In this article, we report on our experience regarding devising, implementing, and deploying a scheduler for multi-source fusion in the context of SCADA systems (Supervisory Control and Data Acquisition). They are challenging because they commonly rely on low-end boards with very limited computing, memory, and storage capabilities, but have to run hundreds if not thousands of agents that co-ordinate by means of complex multi-way rendez-vouses. Our work was carried out in the context of a solar plant in which we could easily confirm that not scheduling the rendez-vouses fairly may easily drive the system into as many as 3 779.10 critical-failure states per hour, whereas a straightforward solution to the problem can reduce the figure to 1 094.76 critical-failure states per hour. Unfortunately, that is far from zero, which is the ideal number. In the literature, there are several proposals to deal with this problem, but most of them could not be adapted to our context, namely: some of them can deal with two-way rendez-vouses only, whereas ours involve an average of 12.89 agents; others require to instrument the agents, but many of them are hardware devices that cannot be modified; a few others cannot work with rendez-vouses that can get intermittently enabled and disabled along an execution, which makes them of little interest in our context; and some require to use shared memory, which is an advanced hardware feature that is not supported by our low-end computing boards. The two proposals that we managed to adapt were not efficient enough in our context since they led to an average of 1 102.77 and 1 458.65 critical-failure states per hour, respectively. That motivated us to work on a new proposal that does not have any of the previous problems. It relies on a incremental approach that was implemented very efficiently using bounded counters and queues. Furthermore, the experimental results and the corresponding statistical analysis confirm that it works very well in practice.

This letter reports the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as delivery systems that could potentially encapsulate and improve the administration of radiotherape...

We consider the evolutionary scheme of morality proposed by Tomasello to defend the idea that the ability to orient the learning of offspring using signs of approval/disapproval could be a decisive and necessary step in the evolution of human morality. Those basic forms of intentional evaluative feedback, something we have called assessor teaching, allow parents to transmit their accumulated experience to their children, both about the behaviors that should be learned as well as how they should be copied. The rationale underlying this process is as follows: if a behavior is approved, then it is good; if it is disapproved, then it is bad. The evaluative guidance on how to behave most probably spread among peers in situations of mutual benefit, such as cooperative child rearing. We argue that our hominin ancestors provided with this capacity for assessor teaching were ideally positioned to develop the two specifically human levels of morality proposed by Tomasello: the morality of fairness and the morality of justice. Assessor teaching could have facilitated the genesis of rudimentary codes of behavior tied with the need to agree about how to behave to succeed in joint cooperative activities. Moreover, learning through assessor teaching provides a plausible explanation for the origin of the objectivist and prescriptive dimensions of human morality. First, we emphasize that individuals feel that they evaluate the behavior of others objectively to guide their learning, and, second, we underline the imperative intention that any moral manifestation possesses.

Unwanted targeting of healthy organs caused by the relocation of radionuclides from the target site has been one of the limiting factors in the widespread application of targeted alpha therapy in patient regimens. GdVO4 nanoparticles (NPs) were developed as platforms to encapsulate α-emitting radionuclides 223Ra, 225Ac, and 227Th, and retain their decay daughters at the target site. Polycrystalline GdVO4 NPs with different morphologies and a zircon-type tetragonal crystal structure were obtained by precipitation of GdCl3 and Na3VO4 in aqueous media at room temperature. The ability of GdVO4 crystals to host multivalent ions was initially assessed using La, Cs, Bi, Ba, and Pb as surrogates of the radionuclides under investigation. A decrease in Ba encapsulation was obtained after increasing the concentration of surrogate ions, whereas the encapsulation of La cations in GdVO4 NPs was quantitative (∼100%). Retention of radionuclides was assessed in vitro by dialyzing the radioactive GdVO4 NPs against deionized water. While 227Th was quantitatively encapsulated (100%), a partial encapsulation of 223Ra (∼75%) and 225Ac (>60%) was observed in GdVO4 NPs. The maximum leakage of 221Fr (1st decay daughter of 225Ac) was 55.4 ± 3.6%, whereas for 223Ra (1st decay daughter of 227Th) the maximum leakage was 73.0 ± 4.0%. These results show the potential of GdVO4 NPs as platforms of α-emitting radionuclides for their application in targeted alpha therapy.

In insect vectors of disease, male and female molecules that mediate reproductive processes are promising targets to suppress fertility of these populations. One process, the storage of sperm in the female reproductive tract, is essential for optimal fertility in all organisms examined to date. In the dengue vector mosquito Aedes aegypti, female sperm storage has not been fully characterized, a requirement to identify sex-specific molecules that mediate this process. Aedes aegypti males deposit the ejaculate into the bursa of the female reproductive tract, and sperm enter the spermathecae—the long-term storage sites—quickly after insemination. However, the proportion of sperm received during mating that are stored in the spermathecae is unclear, and the fate of non-stored sperm unknown. We quantified sperm storage in two Ae. aegypti strains, mated in all combinations, and in two contexts (mass mated and when mating was observed) at 1-, 3- and 5-days post-mating. Sperm quantity in the spermathecae was similar at all timepoints; most females stored ~400 sperm on average. Sperm that did not enter the spermathecae remained in the bursa, where they declined in number and became more fragile to mechanical manipulation at each timepoint. Further, sperm viability in the bursa fell from 91.6% shortly after mating to 12.2% 24 h later. One day after insemination, ~50% of sperm detected in the female reproductive tract was stored in the spermathecae. When we quantified sperm storage in females mated to males that transferred reduced ejaculate quantities (but still able to induce optimal fertility in their mates), sperm detected in the spermathecae similarly declined; females stored ~50% of the sperm received even as sperm quantities transferred at mating declined. Our results suggest that sperm storage in Ae. aegypti females is influenced by ejaculate volume, and that sperm that do not enter the spermathecae remain in the bursa, where they appear to degrade. The consistent presence of sperm in the bursa, even when males transferred low sperm quantities, suggests that the putative degradation of bursa sperm may play a role in Ae. aegypti female fertility, potentially identifying a novel process in this important vector species.

Aunque cada lenguaje tiene sus particularidades, es posible afirmar que van convergiendo hacia elementos compartidos por todos ellos; de ahí que intentemos partir de esas ideas comunes a los principales lenguajes actuales para ir extrapolando posteriormente conceptos de unos a otros. En este volumen se abordan los conceptos básicos de la programación en general, centrándose particularmente en los fundamentos de Java a partir de dos estilos: el estilo funcional usando streams y el más clásico estilo imperativo usando iterables. El diseño de tipos ocupará un lugar central en este volumen en cuya parte final se incluyen varios ejemplos. El material que conforma el manual procede de la experiencia acumulada tras varios años de enseñanza de la asignatura de Fundamentos de Programación en la Universidad de Sevilla.

Targeted alpha therapy (TAT) offers great promise for treating recalcitrant tumors and micrometastatic cancers. One drawback of TAT is the potential damage to normal tissues and organs due to the relocation of decay daughters from the treatment site. The present study evaluates La(227Th)PO4 core (C) and core +2 shells (C2S) nanoparticles (NPs) as a delivery platform of 227Th to minimize systemic distribution of decay daughters, 223Ra and 211Pb. In vitro retention of decay daughters within La(227Th)PO4 C NPs was influenced by the concentration of reagents used during synthesis, in which the leakage of 223Ra was between 0.4 ± 0.2% and 20.3 ± 1.1% in deionized water. Deposition of two nonradioactive LaPO4 shells onto La(227Th)PO4 C NPs increased the retention of decay daughters to >99.75%. The toxicity of the nonradioactive LaPO4 C and C2S NP delivery platforms was examined in a mammalian breast cancer cell line, BT-474. No significant decrease in cell viability was observed for a monolayer of BT-474 cells for NP concentrations below 233.9 μg mL−1, however cell viability decreased below 60% when BT-474 spheroids were incubated with either LaPO4 C or C2S NPs at concentrations exceeding 29.2 μg mL−1. La(227Th)PO4 C2S NPs exhibit a high encapsulation and in vitro retention of radionuclides with limited contribution to cellular cytotoxicity for TAT applications.

Composites containing WO3 or HfO2 nanoparticles were prepared and investigated as alternative shielding materials. Their performance was assessed using radioactive sources emitting photons with energies between 122 and 1407 keV. At 122 keV, the mass attenuation coefficient of the nanocomposites was five times greater to that of the epoxy matrix, and it gradually decreased with increasing energy. An enhancement in the mass attenuation coefficient of the polymer between 15% and 50% was observed at E > 1 MeV when adding the nanoparticles. These results support the development of lightweight garments for radiological application made of nanomaterials and polymeric matrices.

Semantic labelling refers to the problem of assigning known labels to the elements of structured information from a source such as an HTML table or an RDF dump with unknown semantics. In the recent years it has become progressively more relevant due to the growth of available structured information in the Web of data that need to be labelled in order to integrate it in data systems. The existing approaches for semantic labelling have several drawbacks that make them unappealing if not impossible to use in certain scenarios: not accepting nested structures as input, being unable to label structural elements, not being customisable, requiring groups of instances when labelling, requiring matching instances to named entities in a knowledge base, not detecting numeric data, or not supporting complex features. In this article, we propose TAPON-MT, a framework for machine learning semantic labelling. Our framework does not have the former limitations, which makes it domain-independent and customisable. We have implemented it with a graphical interface that eases the creation and analysis of models, and we offer a web service API for their application. We have also validated it with a subset of the National Science Foundation awards dataset, and our conclusion is that TAPON-MT creates models to label information that are effective and efficient in practice.

Human beings have generated a system of cumulative cultural learning with great adaptive value. The evolution of this system required an increase in the capacity to innovate and to imitate in hominin lineage. However that development is costly and, moreover, imitation may restrain the adaptive advantage of a greater investment on innovation. We suggest that a possible way to overcome this problem in hominin evolution was parental teaching by evaluative feedback - i.e. assessor teaching. To explore this hypothesis we developed a mathematical model of cumulative cultural learning. We consider two cognitive levels, one Basic, with less ability to imitate and innovate, and the other Smart, with more ability of both. We study the transition from Basic to Smart in the absence or in presence of teaching. We also study the transition from no teaching to teaching at each cognitive level. We show that the transition to a Smart is easier in a teaching context than in one of only imitation. We also show that the transition to teaching is easier the greater the cognitive level.

Promising alternatives to increase the degradation of dyes in polluted water are radiation and the addition of particulate materials as catalysts. Specifically, gold particles have demonstrated an enhancement of dye degradation in the presence of UV light and/or reducing agents by increasing the rate at which reactive oxygen species are produced. Herein, the enhanced decomposition of methylene blue (MB) under ionizing radiation, X-rays, in the presence of gold particles was investigated. The influence of X-ray operating voltage, gold particle size distribution, and gold concentration in the degradation of MB was studied. Irradiation of MB was performed at a dose rate of ~35 Gy/min and X-ray irradiator operating voltages of 50 kV, 100 kV, and 225 kV. The presence of spherical gold microparticles enhanced the reaction rate of MB up to 61.7%. Results showed that dye degradation combining ionizing radiation and a catalyst such as gold particles is a promising methodology to accelerate the clean-up process of polluted water resources.

Genomic selection (GS) is now practiced successfully across many species. However, many questions remain, such as long-term effects, estimations of genomic parameters, robustness of genome-wide association study (GWAS) with small and large datasets, and stability of genomic predictions. This study summarizes presentations from the authors at the 2020 American Society of Animal Science (ASAS) symposium. The focus of many studies until now is on linkage disequilibrium between two loci. Ignoring higher-level equilibrium may lead to phantom dominance and epistasis. The Bulmer effect leads to a reduction of the additive variance; however, the selection for increased recombination rate can release anew genetic variance. With genomic information, estimates of genetic parameters may be biased by genomic preselection, but costs of estimation can increase drastically due to the dense form of the genomic information. To make the computation of estimates feasible, genotypes could be retained only for the most important animals, and methods of estimation should use algorithms that can recognize dense blocks in sparse matrices. GWASs using small genomic datasets frequently find many marker-trait associations, whereas studies using much bigger datasets find only a few. Most of the current tools use very simple models for GWAS, possibly causing artifacts. These models are adequate for large datasets where pseudo-phenotypes such as deregressed proofs indirectly account for important effects for traits of interest. Artifacts arising in GWAS with small datasets can be minimized by using data from all animals (whether genotyped or not), realistic models, and methods that account for population structure. Recent developments permit the computation of P-values from genomic best linear unbiased prediction (GBLUP), where models can be arbitrarily complex but restricted to genotyped animals only, and single-step GBLUP that also uses phenotypes from ungenotyped animals. Stability was an important part of nongenomic evaluations, where genetic predictions were stable in the absence of new data even with low prediction accuracies. Unfortunately, genomic evaluations for such animals change because all animals with genotypes are connected. A top-ranked animal can easily drop in the next evaluation, causing a crisis of confidence in genomic evaluations. While correlations between consecutive genomic evaluations are high, outliers can have differences as high as 1 SD. A solution to fluctuating genomic evaluations is to base selection decisions on groups of animals. Although many issues in GS have been solved, many new issues that require additional research continue to surface.

Este texto es fruto de la reflexión, la observación y el análisis permanente por parte de los investigadores de los diferentes aportes que el Ejército Nacional hizo a la legitimidad del Estado durante episodios clave del siglo xix, inicios del siglo xx, la guerra con el Perú y la contemporaneidad. Es un esfuerzo intelectual fundamental para la memoria histórica y los relatos sobre los que se construye la identidad nacional 200 años después de la gesta libertadora. Así mismo, esta obra representa un trabajo de investigación formidable, hecho con esfuerzo y profesionalismo, mediante el cual no solo se describe la evolución del Ejército Nacional en estos dos siglos, sino que también se analizan los retos que esta Fuerza ha tenido que enfrentar para poder cumplir la misión permanente e irrenunciable de la defensa de la patria, sus ciudadanos y sus instituciones. En definitiva, la razón que inspira este libro no es otra que el interés por aportar al análisis estratégico del país.

This paper focuses on the difficulty for university students to acquire, within computational thinking, the skills to solve certain problems through recursion. The acquisition of this type of reasoning is essential to understand the different problem solving techniques that are based on recursive algorithms, such as divide and conquer or dynamic programming. Therefore, first, the generalization of problems is proposed as a strategy for designing recursive algorithms. As a second step, that generalization is formalized through a specification sheet that contains different fields that correspond to the characteristics that are relevant to solve a problem recursively.

According to the dual inheritance theory, cultural learning in our species is a biased and highly efficient process of transmitting cultural traits. Here we define a model of cultural learning where social learning is integrated as a complementary element that facilitates the discovery of a specific behavior by an apprentice, and not as a mechanism that works in opposition to individual learning. In that context, we propose that the emergence of the ability to approve or disapprove of offspring behavior, orienting their learning (a process we call assessor teaching), transformed primate social learning into a cultural transmission system, like that which characterizes our species. Assessor teaching facilitates the replication and/or reconstruction of behaviors that are difficult to imitate and helps to determine which behaviors should be imitated. We also explore the form in which assessor teaching has conditioned the evolution of our abilities to develop cultures in the hominin line, converting us into individuals equipped with what we call a suadens psychology. Our main point is to defend the hypothesis that suadens psychology determines the stability and dynamics that affect the trajectories of many cultural characters. We compare our proposal with other theories about cultural evolution, specifically with dual inheritance theory and cultural attraction theory.

A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained and evaluated as calpain inhibitors. The hybrid compounds were inactive, whereas some members of the initial azolomethylideneimidazolone series showed interesting calpain inhibitory activity. By using 4b as a hit compound, a new series of analogs were synthesized by an efficient synthetic procedure based on a multicomponent reaction followed by an unprecedented reaction at the methylene position of the molecule. The best inhibitor found for calpain I (IC50 = 20 nM) was about 20 times more potent than the hit compound. Studies on 4b showed that its inhibition is consistent with an uncompetitive inhibition mode. This compound did not exhibit cellular toxicity at any of the doses tested (0.1–10 μM) and further studies indicated that it was capable of blockading chemical ischemia induction of apoptosis by preventing sodium azide-dependent calpain activation in intact human kidney tubular epithelial cells. The results of molecular modeling studies rationalized the inhibitory activity found for this series and account, from a structural point of view, for the most active compound identified (4j).

Achieving efficiency both in terms of resource utilisation and energy consumption is a complex challenge, especially in large-scale wide-purpose data centers that serve cloud-computing services. Simulation presents an appropriate solution for the development and testing of strategies that aim to improve efficiency problems before their applications in production environments. Various cloud simulators have been proposed to cover different aspects of the operation environment of cloud-computing systems. In this paper, we define the SCORE tool, which is dedicated to the simulation of energy-efficient monolithic and parallel-scheduling models and for the execution of heterogeneous, realistic and synthetic workloads. The simulator has been evaluated through empirical tests. The results of the experiments confirm that SCORE is a performant and reliable tool for testing energy-efficiency, security, and scheduling strategies in cloud-computing environments.

Radiolytic synthesis has been used to produce a plethora of unsupported and supported metallic nanoparticles in batch. As proof of a new concept, we evaluated the formation of gold nanoparticles by radiolytic synthesis in continuous flow using a millifluidic reactor. A mixture of gold ions solution, branched polyethyleneimine, and ethylene glycol yielded gold nanoparticles with a mean size of 3.4 ± 1.0 nm after irradiation with an X-ray irradiator (127 Gy/min) at an absorbed dose of 5.1 kGy. The morphology and size distribution of gold nanoparticles was influenced by AgNO3, where its absence resulted in a mean size of 20.9 ± 15.8 nm. The radiolytic synthesis of gold nanoparticles in continuous flow was achieved in short reaction times (

Insulin receptor substrate 4 (IRS-4) is an adaptor protein for which new evidence suggests plays a role in tumour promotion. We described nuclear IRS-4 in RKO colon cancer cell lines in biopsies of patients with colorectal cancer (CRC) (n = 20) and in matched adjacent normal colorectal (MANC) tissue (n = 20). Treatment with physiological doses of IGF-1 promoted nuclear influx of IRS-4 from cellular cytosol in RKO cells. When exogenous IRS-4 was overexpressed in RKO cells, there was an increase in cyclin D1, cyclin E, E2F1, pRB Ser 809/811 and pRB Ser 705 levels compared with the empty vector-transfected cells. Some of these changes returned to control values after wortmannin treatment. Subcellular fractionation showed an overexpression of IRS-4 in the cytoplasm, membrane, and nuclei of tumour samples, whereas the levels of the protein were barely detectable in the three compartments of normal samples. Immunohistochemical studies showed positive nuclear IRS-4 staining in over 74% of the tumour cells. IRS-4 was strongly overexpressed in tumoural tissues from CRC patients compared to MANC tissues. The up-regulation of IRS-4 in CRC samples correlated significantly with the increase of several G1 checkpoint proteins including cyclin D1 (r = 0.6662), Rb (r = 0.7779), pRb Serine 809/811 (r = 0.6864), pRb serine 705 (r = 0.6261) and E2F1 (r = 0.8702). Taken together, our findings suggest that IRS-4 promotes retinoblastoma–cyclin-dependent kinase activation and it may serve as a pharmacological target since its expression is very low in normal tissue, including colonic epithelium.

Gadolinium vanadate nanoparticles (NPs) doped with europium, in concentrations between 5-40%, were synthesized via an aqueous route to prove their multimodal imaging functionalities and their performance as radionuclide carriers for targeted alpha therapy. Core-shell Gd0.8Eu0.2VO4 NPs were doped with the α-emitting actinium-225 to assess the in vitro retention of 225Ac and its decay daughters; francium-221 and bismuth-213. Gd0.8Eu0.2VO4 core-shell NPs were obtained using a precipitation synthesis route having a tetragonal system, a spherical morphology, and a uniform particle size distribution. Gd0.8Eu0.2VO4 core-shell NPs displayed the characteristic intense emission at 618 nm (red) and paramagnetic behavior of Eu and Gd cations, respectively. Partial retention of radionuclides was obtained with Gd0.8Eu0.2VO4 core NPs, while deposition of two nonradioactive Gd0.8Eu0.2VO4 shells significantly decreased the leakage of both 225Ac and 221Fr. The luminescence and magnetic functionalities as well as radionuclide retention capabilities of Gd0.8Eu0.2VO4 core-shell NPs demonstrate their potential for biomedical applications.

8 Pág. Departamento de ​Mejora Genética Animal, A common type of rearing in aquaculture selective breeding programs is to keep families in separate tanks until fish is large enough to be individually tagged. This type of rearing introduces an environmental effect common to the members of the same family which can be difficult to be disentangled from genetic effects when traditional BLUP evaluation is used. The use of genomic evaluation could lead to a better prediction of these effects as markers can capture more accurately genetic relationships between fish raised in different tanks and between full-sibs raised in the same tank. The objective of this simulation study was to predict the benefit of genomic evaluation (GBLUP) when compared to BLUP in the presence of common environmental effects. Models that included or excluded these effects when they were present were compared. Populations with two different levels of linkage disequilibrium were generated. The heritability of the selected trait was 0.4 and three different proportions of phenotypic variance due to common environmental effect (0.0, 0.1 and 0.3) were considered. Nested mating designs where each male was mated to two females were simulated to create 200 full-sib families with 10 or 50 fish per family. GBLUP was less affected than BLUP by the presence of common environmental effects. The loss in genetic gain ranged from 0% to 4% with GBLUP and from 2% to 7% with BLUP. As a consequence, the benefit of GBLUP increased in the presence of common environmental effects, and the extra benefit increased with increasing linkage disequilibrium and family size. In the absence of these effects, genetic gain from GBLUP was up 20% higher than from BLUP and in their presence, genetic gain from GBLUP was 27% higher than from BLUP. Although GBLUP always led to lower inbreeding than BLUP, there were no extra benefits in terms of extra reductions in the presence of common environmental effects. Finally, when these effects were present but ignored in the evaluation model, the loss in genetic gain was moderate but inbreeding increased dramatically, particularly in BLUP scenarios., The research leading to these results has received funding from the Instituto Nacional de Investigacion y Tecnología Agraria y Alimentaria (FPI-SGIT2016-02), the European Union's Seventh Framework Program (KBBE.2013.1.2-10) under grant agreement n◦ 613611, the Ministerio de Ciencia e Innovacion, ´ Spain (grant CGL2016-75904-C2-2-P and PID2020-114426GB-C22) and from the European Commission Horizon 2020 (H2020) Framework Programme through grant agreement no 727315 MedAID project (Mediterranean Aquaculture Integrated Development).

Predictive monitoring of business processes is a challenging topic of process mining which is concerned with the prediction of process indicators of running process instances. The main value of predictive monitoring is to provide information in order to take proactive and corrective actions to improve process performance and mitigate risks in real time. In this paper, we present an approach for predictive monitoring based on the use of evolutionary algorithms. Our method provides a novel event window-based encoding and generates a set of decision rules for the run-time prediction of process indicators according to event log properties. These rules can be interpreted by users to extract further insight of the business processes while keeping a high level of accuracy. Furthermore, a full software stack consisting of a tool to support the training phase and a framework that enables the integration of run-time predictions with business process management systems, has been developed. Obtained results show the validity of our proposal for two large real-life datasets: BPI Challenge 2013 and IT Department of Andalusian Health Service (SAS).

Genomic prediction methods based on multiple markers have potential to include nonadditive effects in prediction and analysis of complex traits. However, most developments assume a Hardy–Weinberg equilibrium (HWE). Statistical approaches for genomic selection that account for dominance and epistasis in a general context, without assuming HWE (e.g., crosses or homozygous lines), are therefore needed. Our method expands the natural and orthogonal interactions (NOIA) approach, which builds incidence matrices based on genotypic (not allelic) frequencies, to include genome-wide epistasis for an arbitrary number of interacting loci in a genomic evaluation context. This results in an orthogonal partition of the variances, which is not warranted otherwise. We also present the partition of variance as a function of genotypic values and frequencies following Cockerham’s orthogonal contrast approach. Then we prove for the first time that, even not in HWE, the multiple-loci NOIA method is equivalent to construct epistatic genomic relationship matrices for higher-order interactions using Hadamard products of additive and dominant genomic orthogonal relationships. A standardization based on the trace of the relationship matrices is, however, needed. We illustrate these results with two simulated F1 (not in HWE) populations, either in linkage equilibrium (LE), or in linkage disequilibrium (LD) and divergent selection, and pure biological dominant pairwise epistasis. In the LE case, correct and orthogonal estimates of variances were obtained using NOIA genomic relationships but not if relationships were constructed assuming HWE. For the LD simulation, differences were smaller, due to the smaller deviation of the F1 from HWE. Wrongly assuming HWE to build genomic relationships and estimate variance components yields biased estimates, inflates the total genetic variance, and the estimates are not empirically orthogonal. The NOIA method to build genomic relationships, coupled with the use of Hadamard products for epistatic terms, allows the obtaining of correct estimates in populations either in HWE or not in HWE, and extends to any order of epistatic interactions.

Effective population size is a key parameter in conservation genetics. In the management of conservation programs using pedigree information, there is a consensus that the optimal method for maximizing effective population size is to calculate the contribution of each potential parent (the number of offspring that each individual leaves to the next generation) by minimizing the global pedigree-based coancestry between potential parents weighted by their contributions. When using molecular data, the optimal method for managing genetic diversity will remain the same but now the molecular coancestry calculated from markers will replace the pedigree-based coancestry. However, in this situation, the concept of effective population size loses its meaning because with optimal molecular management, genetic diversity increases in early generations and therefore effective population size takes negative values. Furthermore, in the long term, the molecular effective population size does not attain an asymptotic value but it shows an unpredictable behaviour.

Ruthenium nanoparticles on pristine (MWCNT) and functionalized carbon nanotubes (f-MWCNT), and graphene oxide have been prepared through a facile, single step radiolytic method at room temperature, and ambient pressure. This synthesis process relies on the interaction of high energy gamma rays from a 60 Co source with the water in the aqueous solutions containing the Ru precursor, leading to the generation of highly reducing species that further reduce the Ru metal ions to zero valence state. Transmission electron microscopy and X-Ray diffraction revealed that the nanoparticles were homogeneously distributed on the surface of the supports with an average size of ∼2.5 nm. X-ray Photoelectron spectroscopy analysis showed that the interaction of the Ru nanoparticles with the supports occurred through oxygenated functionalities, creating metal-oxygen bonds. This method demonstrates to be a simple and clean approach to produce well dispersed nanoparticles on the aforementioned supports without the need of any hazardous chemical.

Lanthanide phosphate nanomaterials are appealing as multifunctional platforms for biomedical applications because of their low toxicity, radiation resistance, and unique luminescence and magnetic properties. Lanthanide phosphate nanoparticles (NPs) radiolabeled with 156Eu were synthesized by an aqueous route using sodium tripolyphosphate as a phosphate source and complexing agent. GdPO4 was used as a host matrix, while synthetic concentrations of Ce3+/Tb3+ and Eu3+ were varied between 5–40% and 10–30%, respectively, and yielded spherical NPs with hexagonal crystal system and particle size 90% was achieved for GdPO4 and Gd0.6Ce0.3Tb0.1PO4 NPs intrinsically radiolabeled with 156Eu. In vitro retention of 156Eu within LnPO4 NPs was > 97% over 3 weeks. Intrinsically radiolabeled LnPO4 NPs have the potential to combine the luminescence and magnetic properties of Ln3+ ions with lanthanide radioisotopes for biomedical and environmental applications.

The availability of dense panels of common single-nucleotide polymorphisms and sequence variants has facilitated the study of statistical features of the genetic architecture of complex traits and diseases via whole-genome regressions (WGRs). At the onset, traits were analyzed trait by trait, but recently, WGRs have been extended for analysis of several traits jointly. The expectation is that such an approach would offer insight into mechanisms that cause trait associations, such as pleiotropy. We demonstrate that correlation parameters inferred using markers can give a distorted picture of the genetic correlation between traits. In the absence of knowledge of linkage disequilibrium relationships between quantitative or disease trait loci and markers, speculating about genetic correlation and its causes (e.g., pleiotropy) using genomic data is conjectural.

Mediterranean mussel (Mytilus galloprovincialis) is one of the main species of the European aquaculture, Galicia being (NW Spain) the main productive region (~ 200,000 t/year). The main problem for mussel production is the accumulation of toxins coming from microalgae blooms, which have even increased in recent years determining the banning of commercialization for long periods. We estimated the heritability and correlations (genetic and phenotypic) for toxin concentration after a toxic episode related to the main diarrheic toxin, okadaic acid, and after a depuration period at indoor facilities using a large amount of full-sib (170) and half-sib families (above 600 both via father and via mother). We took advantage of the experimental design to estimate the same parameters for other relevant traits for mussel production like growth-related traits and color. Heritabilities were moderate and significant after both the accumulation and detoxification periods (h2 ~ 0.35), suggesting the possibility of reducing toxin concentration through breeding programs in mussels. Growth-related traits also showed moderate heritabilities (~ 0.30), while color showed a very high heritability (~ 0.90), making them suitable for selection depending on producer and consumer demands. Interestingly, growth-related traits showed negative and significant genetic and phenotypic correlations with toxin concentration, while color showed positive ones, strongly suggesting that bigger and whitish mussels may accumulate less toxin. The results of our study support the viability of breeding programs to face the main problems of mussel industry, but this approach will determine a change in seed production, the wild seed being replaced or complemented with hatchery-produced seed.

RESUMO Objetivos: Analisar a associação entre os níveis glicêmicos quando da admissão dos pacientes à unidade de terapia intensiva pediátrica e a mortalidade entre pacientes hospitalizados. Métodos: Estudo retrospectivo de coorte conduzido em pacientes de uma unidade de terapia intensiva, admitidos ao Instituto Nacional de Salud del Niño entre 2012 e 2013. Utilizou-se um modelo de regressão de Poisson com variância robusta para qualificar a associação. Foi feita avaliação do desempenho do exame diagnóstico, para descrever sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e razão de verossimilhança para cada faixa de glicemia. Resultados: Incluíram-se no total 552 pacientes (idade mediana de 23 meses; faixa de variação entre 5 meses e 79,8 meses). O nível glicêmico médio quando da admissão foi de 121,3mg/dL (6,73mmol/L). Faleceram durante a hospitalização 92 (16,6%) pacientes. Na análise multivariada, encontraram-se associações significantes entre glicemia < 65mg/dL (3,61mmol/L) (RR: 2,01; IC95% 1,14 - 3,53), glicemia > 200mg/dL (> 11,1mmol/L) (RR: 2,91; IC95% 1,71 - 4,55), desnutrição (RR: 1,53, IC95% 1,04 - 2,25), ventilação mecânica (RR: 3,71, IC95% 1,17 - 11,76) e mortalidade durante a hospitalização. Ocorreram baixa sensibilidade (entre 17,39% e 39,13%) e alta especificidade (entre 49,13% e 91,74%) para diferentes níveis glicêmicos de corte. Conclusão: Ocorreu maior risco de óbito entre os pacientes que desenvolveram hipoglicemia e hiperglicemia por ocasião da admissão à unidade de terapia intensiva pediátrica. Certas faixas de glicemia (> 200mg/dL (> 11,1mmol/L) e < 65mg/dL (3,61mmol/L)) tiveram uma alta especificidade como preditores de óbito. ABSTRACT Objectives: To analyze the association between glycemia levels upon pediatric intensive care unit admission and mortality in patients hospitalized. Methods: A retrospective cohort of pediatric intensive care unit patients admitted to the Instituto Nacional de Salud del Niño between 2012 and 2013. A Poisson regression model with robust variance was used to quantify the association. Diagnostic test performance evaluation was used to describe the sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios for each range of glycemia. Results: In total, 552 patients were included (median age 23 months, age range 5 months to 79.8 months). The mean glycemia level upon admission was 121.3mg/dL (6.73mmol/L). Ninety-two (16.6%) patients died during hospitalization. In multivariable analyses, significant associations were found between glycemia < 65mg/dL (3.61mmol/L) (RR: 2.01, 95%CI 1.14 - 3.53), glycemia > 200mg/dL (> 11.1mmol/L) (RR: 2.91, 95%CI 1.71 - 4.55), malnutrition (RR: 1.53, 95%CI 1.04 - 2.25), mechanical ventilation (RR: 3.71, 95%CI 1.17 - 11.76) and mortality at discharge. There was low sensitivity (between 17.39% and 39.13%) and high specificity (between 49.13% and 91.74%) for different glucose cut-off levels. Conclusion: There was an increased risk of death at discharge in patients who developed hypoglycemia and hyperglycemia upon admission to the pediatric intensive care unit. Certain glucose ranges (> 200mg/dL (> 11.1mmol/L) and < 65mg/dL (3.61mmol/L)) have high specificity as predictors of death at discharge.

We developed a general farmer socioeconomic typology to help in analyzing the herd dynamics and farmers' decision making and in designing strategies for the development of local animal breeds. The typology was built on few measurable socioeconomic factors that are often used as indicators of the economic and cultural capital of farmers. We used a sample of 85 farmers of the Spanish Avileña-Negra Ibérica (ANI) local cattle breed to illustrate and test the procedure. The farmer types were defined by a hierarchical cluster analysis with a set of canonical variables derived from five socioeconomic factors formal educational level and age of a farmer, year since the farmer started keeping the ANI breed, percentage of the total household income covered by the farm and percentage of the total farm land owned by the farmer. Five farmer types were determined based on the formal educational level of a farmer and on the percentage of the total household income covered by the farm (1) Land owners, medium educated; (2) Owners of part of the farm land, low educated; (3) Owners of part of the farm land, high educated; (4) Landless farmers, medium educated; and (5) Landless farmers, low educated. The farmer types were found to be linked to several other attributes used in summarising farm profiles. The farmer types also differed in how farmers make farm management decisions about herd size and breed composition, breeding aims and collaborative activities with other farmers. In addition, the farmer types had a variable dependency on subsidy payments suggesting that the changes in subsidy programme will lead to a redistribution of farmers across the types. We conclude that typologies based on farmers' cultural and economic capital, could be a useful tool to foresee farmers' decision-making concerning the on-farm breed development. © 2014 Elsevier B.V.

Gadolinium vanadate (GdVO4) core and core + 2 shell nanocrystals (NCs) were evaluated for in vitro retention of 225Ac, 227Th, and their first decay daughters, 221Fr and 223Ra, respectively. GdVO4 NCs with a tetragonal crystal system (zircon-type) and spherical morphology were obtained by precipitation of GdCl3 and Na3VO4 using sodium citrate as a complexing agent. The growth of two nonradioactive GdVO4 shells on both Gd(225Ac)VO4 and Gd(227Th)VO4 core NCs was demonstrated by an increase of 0.7 nm and 2 nm in the crystallite size, respectively. The maximum leakage of 225Ac was 15% and 2.4% from core and core + 2 shells, whereas the leakage of 227Th was 3% and 1.5%, respectively. The presence of two nonradioactive GdVO4 shells increased the retention of 221Fr and 223Ra by 20% and 15% with respect to core NCs. Furthermore, a longitudinal proton relaxivity, r1 = 0.9289 s−1 mM−1, confirmed their potential application as contrast agents for magnetic resonance imaging. In summary, GdVO4 NCs show promising capabilities as radionuclide carriers with partial retention of decay daughters and as contrast agents for theranostic applications.

Cloud computing paradigm has brought an overwhelming variety of cloud services from different providers, each one offering a plethora of configuration and purchasing options for them. Users may have certain requirements and preferences not only concerning service configuration, but also with respect to their usage schedule. In this situation, an appropriate provisioning plan considering all restrictions would help users to achieve their goals while taking into account the different available providers, their pricing and even the usage discounts they provide. In this work, we describe an automated solution that analyzes user needs that include scheduling restrictions to obtain optimized provisioning plans for different cloud providers, which allow users to compare several offerings that possibly consider volume or usage discounts. We validate this solution against a realistic use case, while also providing a prototype implementation in the form of publicly available microservices. Ministerio de Economia y Competitividad TIN2015-70560-R Junta de Andalucía P12-TIC-1867

Process performance indicators (PPIs) allow the quantitative evaluation of business processes, providing essential information for decision making. It is common practice today that business processes and PPIs are usually modelled separately using graphical notations for the former and natural language for the latter. This approach makes PPI definitions simple to read and write, but it hinders maintenance consistency between business processes and PPIs. It also requires their manual translation into lower-level implementation languages for their operationalisation, which is a time-consuming, error-prone task because of the ambiguities inherent to natural language definitions. In this article, VISUAL PPINOT, a graphical notation for defining PPIs together with business process models, is presented. Its underlying formal metamodel allows the automated processing of PPIs. Furthermore, it improves current state-of-the-art proposals in terms of expressiveness and in terms of providing an explicit visualisation of the link between PPIs and business processes, which avoids inconsistencies and promotes their co-evolution. The reference implementation, developed as a complete tool suite, has allowed its validation in a multiple- case study, in which five dimensions of VISUAL PPINOT were studied: expressiveness, precision, automation, understandability, and traceability. Comisión Interministerial de Ciencia y Tecnología TIN2015-70560-R Junta de Andalucía P12-TIC-1867

In aquaculture breeding programmes, selection within families cannot be applied for traits that cannot be recorded on the candidates (e.g.;disease resistance or fillet quality). However, this problem can be overcome if genomic evaluation is used. Within-family genomic evaluation has been proposed for these programmes as large family sizes are available and substantial levels of linkage disequilibrium (LD) within families can be attained with a limited number of markers even in populations in global linkage equilibrium. Here, we compare by computer simulation (i) within-family and population-wide LD; and (ii) the accuracy of within-family genomic selection when genomic evaluations are carried out either at the population level or within families. The population simulated was composed by a varying number of families of full-sibs (half for training and half for testing). The results indicate that, to practice within-family selection, performing the genomic evaluation separately for each family using only molecular information from the family could be recommended for populations either in linkage equilibrium or with a low level of disequilibrium. © 2017 Blackwell Verlag GmbH

Defeasible argumentation is typical of legal and scientific reasoning. A defeasible argument is one in which the conclusion can be accepted tentatively in relation with the evidence known so far, but may need to be retracted as new evidence comes in. This paper analyses the role of defeasible argumentation in the explanation and evaluation of architectural decisions. We analyse technical explanations offered by engineers at Twitter and eBay about several architectural decisions adopted in those systems. We generalize these examples in four argumentation schemes. We also study the typical case of reasoning with a formal model of an architecture, and we infer a fifth argumentation scheme. Finally, we apply Hastings’ method of attaching a set of critical questions to each scheme. We show that the existence of critical questions reveals that the inferred schemes are defeasible: in argumentation theory, if a respondent asks one of the critical questions matching a scheme and the proponent of an argument fails to offer an adequate answer, the argument defaults and the conclusion is retracted. This dialogical structure is the basis of typical architectural evaluations. We conclude that the provided evidence supports the hypothesis that defeasible argumentation is employed in architectural evaluation. In this context, a rich catalogue of argumentation schemes is a useful tool for the architect to organize his or her reasoning; critical questions assist the architect in identifying the weak points of his or her explanations, and provide the evaluation team with a checklist of issues to be raised. Universidad de Sevilla VPPI-US

Current aquaculture breeding programs aimed at improving resistance to diseases are based on challenge tests, where performance is recorded on sibs of candidates to selection, and on selection between families. Genome-wide evaluation (GWE) of breeding values offers new opportunities for using variation within families when dealing with such traits. However, up-to-date studies on GWE in aquaculture programs have only considered continuous traits. The objectives of this study were to extend GWE methodology, in particular the Bayes B method, to analyze dichotomous traits such as resistance to disease, and to quantify, through computer simulation, the accuracy of GWE for disease resistance in aquaculture sib-based programs, using the methodology developed. Two heritabilities (0.1 and 0.3) and 2 disease prevalences (0.1 and 0.5) were assumed in the simulations. We followed the threshold liability model, which assumes that there is an underlying variable (liability) with a continuous distribution and assumed a BayesB model for the liabilities. It was shown that the threshold liability model used fits very well with the BayesB model of GWE. The advantage of using the threshold model was clear when dealing with disease resistance dichotomous phenotypes, particularly under the conditions where linear models are less appropriate (low heritability and disease prevalence). In the testing set (where individuals are genotyped but not measured), the increase in accuracy for the simulated schemes when using the threshold model ranged from 4 (for heritability equal to 0.3 and prevalence equal to 0.5) to 16% (for heritability and prevalence equal to 0.1) when compared with the linear model.

Summary We study here the effect of using genome-wide marker data versus genealogical data in population management for the maintenance of diversity in conservation schemes using optimal contributions. We re-examine the benefits of using molecular data for different population and genome sizes and compare different management strategies according to the group of individuals where we take decisions (parents or offspring). We also study the consequences of using estimated genealogical coancestries calculated from molecular information. Using genome-wide marker data performed usually better than using genealogical data or estimated genealogical coancestry to maintain expected and observed heterozygosity. Furthermore, when we could take decisions acting on the offspring, a larger heterozygosity was maintained than when we based our decisions on the potential parents.

An experiment with mice was designed to test the relative efficiency of three selection methods that help to minimize the rate of inbreeding during selection. A common house mice (Mus musculus) population was selected for 17 generations to increase the weight gain between 21 and 42 days. The population was split at random into three lines A, B and C where three selection methods were applied: individual selection and random mating, weighted selection with random mating and individual selection with minimum coancestry mating, respectively. There were three replicates for each line. Cumulated selection response was similar in the three lines, but there were differences in the level of inbreeding attained (in percentage): 31.24 (method A), 24.72 (method B) and 27.88 (method C). As consequence, lines B and C (weighted selection and minimum coancestry) showed a lower value of deterioration of fitness traits (the intrauterine mortality and the mortality at birth) than line A (random mating).